Canary on a chip: embedded sensors with bio-chemical interfaces

Abstract

Wireless electrochemical measurements methods using minimally invasive micro-sensors that monitor response of cells to specific analytes are described. Micro-actuators integrated on a same chip as the micro-sensors are used to provide closed loop in-vivo local therapy on demand. An in-vivo bio-electronic system that can monitor the health of cell colonies and accordingly dispense corresponding therapeutic drugs is also described.

The invention claimed is: 
     
       1. A wireless body-implantable device comprising:
 an electromagnetic wireless transmit system; 
 an electrochemical sensor monolithically integrated in an electronic chip fabricated on a silicon substrate, connected to the electromagnetic wireless transmit system, and comprising a functionalized layer comprising cell cultures or cell colonies confined within a semi-permeable cell containment barrier; 
 a hermetic package sealed to the silicon substrate, the hermetic package containing a payload and an electrolyte; 
 an actuator element integrated on the silicon substrate configured to heat the electrolyte thereby releasing the hermetic package from the silicon substrate triggering a release of the payload; and 
 electrodes in wells created by etched electrode metals on the electrochemical sensor and within the functionalized layer such that at least a portion of the functionalized layer is in the wells. 
 
     
     
       2. The wireless body-implantable device of  claim 1 , wherein the electrodes are patterned. 
     
     
       3. The wireless body-implantable device of  claim 1 , wherein the semi-permeable containment barrier is an organic pouch. 
     
     
       4. The wireless body-implantable device of  claim 1 , wherein the semi-permeable containment barrier comprises parylene. 
     
     
       5. The wireless body-implantable device of  claim 1 , wherein the cell cultures or colonies are specifically selected for sensing one or more of: a) genomic markers including micro-RNAs and circulating DNAs, and b) exosomes and cytokine molecules in blood, interstitial fluid, urine or saliva. 
     
     
       6. The wireless body-implantable device of  claim 1 , further comprising an optical sensor configured to detect fluorescence emitted by fluorescent protein markers reacting in an analyte. 
     
     
       7. The wireless body-implantable device of  claim 1 , further comprising an electromagnetic wireless receiver system. 
     
     
       8. The wireless body-implantable device of  claim 7 , further comprising a power management system that is configured to receive power for the wireless body-implantable device from an electromagnetic wireless link to the electromagnetic wireless receiver system. 
     
     
       9. The wireless body-implantable device of  claim 1 , wherein the electrodes comprise a noble metal or a noble metal oxide. 
     
     
       10. The wireless body-implantable device of  claim 9 , wherein the noble metal is platinum. 
     
     
       11. The wireless body-implantable device of  claim 1 , wherein the electrochemical sensor and electronic chip are fabricated in a CMOS process. 
     
     
       12. The wireless body-implantable device of  claim 1 , the silicon substrate further comprising an antenna. 
     
     
       13. The wireless body-implantable device of  claim 1 , wherein the hermetic package is a single chamber hermetic package. 
     
     
       14. The wireless body-implantable device of  claim 1 , wherein the electrochemical sensor is fabricated on a front side of the silicon substrate. 
     
     
       15. The wireless body-implantable device of  claim 1 , wherein the functionalized layer is fully embedded within the wells. 
     
     
       16. The wireless body-implantable device of  claim 1 , wherein dimensions of the device are no larger than 1.0 mm×1.0 mm×400 μm. 
     
     
       17. The wireless body-implantable device of  claim 1 , wherein the electrolyte and the payload are in separate chambers of the hermetic package. 
     
     
       18. A wireless body-implantable device comprising:
 an electromagnetic wireless transmit system; 
 a hermetic package sealed to a silicon substrate, the hermetic package containing a payload and an electrolyte; and 
 an electrochemical sensor connected to the electromagnetic wireless transmit system and comprising electrodes in wells created by etched electrode metals on the electrochemical sensor and within a functionalized layer such that at least a portion of the functionalized layer is in the wells, wherein the functionalized layer comprises cell cultures or cell colonies confined within a semi-permeable cell containment barrier, 
 wherein:
 a metabolic reaction of the cell cultures or cell colonies with an analyte of interest releases a chemistry of interest, and the electrochemical sensor senses the released chemistry of interest and actuates a heating element in the silicon substrate, such that the electrolyte heats up, the hermetic package is released from the silicon substrate, releasing the payload from the hermetic package.